This request is for funds to continue studying the mechanisms controlling renin release from the isolated perfused rat kidney. Projects are proposed to answer certain specific questions with the major emphasis being on defining more precisely the stretch receptor mode of controlling renin release. The role of hemodynamic and chemical factors in changing the sensitivity of the stretch receptor will be investigated. The chronic effects of renal denervation will be investigated to determine whether the juxtaglomerular cells behave more like endocrine cells or like smooth muscle cells. The mechanism by which high potassium inhibits renin release will be sought in the context of the stretch receptor model. The mechanism controlling renin release during sodium deprivation will be investigated by producing one non-filtering kidney in the rat and then sodium depriving the animal for four to five days. The kidney will be removed and perfused in isolation. The role played by increased renal renin content during the enhanced renin release observed with sodium deprivation and caval constriction will be sought also. The mechanism of renin release during ureteral occlusion, albumin infusion, and clonidine administration will be investigated. The role played by Ca, Na, and Mg in the stimulus-secretion coupling process will be determined. Whether the factors that stimulate renin release also stimulate renin synthesis or conversion from prorenin to renin will be investigated.